A proteomic investigation of glomerular podocytes from a Denys-Drash Syndrome patient with a mutation in the Wilms tumour suppressor gene WT1
Glomerular podocytes are essential for blood filtration in the kidney underpinned by their unique cytoskeletal morphology. An increasing number of kidney diseases are being associated with key podocyte abnormalities. The Wilms tumour suppressor gene (WT1) encodes a zinc finger protein with a crucial...
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description | Glomerular podocytes are essential for blood filtration in the kidney underpinned by their unique cytoskeletal morphology. An increasing number of kidney diseases are being associated with key podocyte abnormalities. The Wilms tumour suppressor gene (WT1) encodes a zinc finger protein with a crucial role in normal kidney development; and in the adult, WT1 is required for normal podocyte function. Denys‐Drash Syndrome (DDS) results from mutations affecting the zinc finger domain of WT1. The aim of this study was to undertake, for the first time, a proteomic analysis of cultured human podocytes; and to analyse the molecular changes in DDS podocytes. The morphology of DDS podocytes was highly irregular, reminiscent of a fibroblastic appearance. A reference 2‐D gel was generated, and 75 proteins were identified of which 43% involved in cytoskeletal architecture. The DDS and wild‐type proteomes were compared by 2‐D DIGE. The level of 95.6% of proteins was unaltered; but 4.4% were altered more than two‐fold. A sample of proteins involved in cytoskeletal architecture appeared to be misexpressed in DDS podocytes. Consistent with this finding, overall levels of filamentous actin also appeared reduced in DDS podocytes. We conclude that one of WT1 functions in podocytes is to regulate the expression of key components and regulators of the cytoskeleton. |
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An increasing number of kidney diseases are being associated with key podocyte abnormalities. The Wilms tumour suppressor gene (WT1) encodes a zinc finger protein with a crucial role in normal kidney development; and in the adult, WT1 is required for normal podocyte function. Denys‐Drash Syndrome (DDS) results from mutations affecting the zinc finger domain of WT1. The aim of this study was to undertake, for the first time, a proteomic analysis of cultured human podocytes; and to analyse the molecular changes in DDS podocytes. The morphology of DDS podocytes was highly irregular, reminiscent of a fibroblastic appearance. A reference 2‐D gel was generated, and 75 proteins were identified of which 43% involved in cytoskeletal architecture. The DDS and wild‐type proteomes were compared by 2‐D DIGE. The level of 95.6% of proteins was unaltered; but 4.4% were altered more than two‐fold. A sample of proteins involved in cytoskeletal architecture appeared to be misexpressed in DDS podocytes. Consistent with this finding, overall levels of filamentous actin also appeared reduced in DDS podocytes. We conclude that one of WT1 functions in podocytes is to regulate the expression of key components and regulators of the cytoskeleton.</description><identifier>ISSN: 1615-9853</identifier><identifier>EISSN: 1615-9861</identifier><identifier>DOI: 10.1002/pmic.200600666</identifier><identifier>PMID: 17295355</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>2-D DIGE ; Amino Acid Substitution ; Analytical, structural and metabolic biochemistry ; Biological and medical sciences ; Cells, Cultured ; Child ; Cytoskeletal architecture ; Denys-Drash Syndrome ; Denys-Drash Syndrome - genetics ; Denys-Drash Syndrome - metabolism ; Fundamental and applied biological sciences. Psychology ; Humans ; Kidneys ; Medical sciences ; Miscellaneous ; Nephrology. Urinary tract diseases ; Podocytes ; Podocytes - metabolism ; Proteins ; Proteome - metabolism ; Proteomics ; Tumors of the urinary system ; WT1 ; WT1 Proteins - genetics</subject><ispartof>Proteomics (Weinheim), 2007-03, Vol.7 (5), p.804-815</ispartof><rights>Copyright © 2007 WILEY‐VCH Verlag GmbH & Co. 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An increasing number of kidney diseases are being associated with key podocyte abnormalities. The Wilms tumour suppressor gene (WT1) encodes a zinc finger protein with a crucial role in normal kidney development; and in the adult, WT1 is required for normal podocyte function. Denys‐Drash Syndrome (DDS) results from mutations affecting the zinc finger domain of WT1. The aim of this study was to undertake, for the first time, a proteomic analysis of cultured human podocytes; and to analyse the molecular changes in DDS podocytes. The morphology of DDS podocytes was highly irregular, reminiscent of a fibroblastic appearance. A reference 2‐D gel was generated, and 75 proteins were identified of which 43% involved in cytoskeletal architecture. The DDS and wild‐type proteomes were compared by 2‐D DIGE. The level of 95.6% of proteins was unaltered; but 4.4% were altered more than two‐fold. A sample of proteins involved in cytoskeletal architecture appeared to be misexpressed in DDS podocytes. Consistent with this finding, overall levels of filamentous actin also appeared reduced in DDS podocytes. We conclude that one of WT1 functions in podocytes is to regulate the expression of key components and regulators of the cytoskeleton.</description><subject>2-D DIGE</subject><subject>Amino Acid Substitution</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Child</subject><subject>Cytoskeletal architecture</subject><subject>Denys-Drash Syndrome</subject><subject>Denys-Drash Syndrome - genetics</subject><subject>Denys-Drash Syndrome - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Kidneys</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Podocytes</subject><subject>Podocytes - metabolism</subject><subject>Proteins</subject><subject>Proteome - metabolism</subject><subject>Proteomics</subject><subject>Tumors of the urinary system</subject><subject>WT1</subject><subject>WT1 Proteins - genetics</subject><issn>1615-9853</issn><issn>1615-9861</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtu1DAYhSMEoje2LJE3LDP4kjj2sprSoVJvUge6tDzOnxlDEke2Q8lD9J1xldGUHZIlW_b3nd86WfaR4AXBmH4ZOmsWFGOeFudvsmPCSZlLwcnbw7lkR9lJCD8xJpWQ1fvsiFRUlqwsj7PnczR4F8GlHGT73xCi3epoXY9cg7at68CPrfZocLUzU4SAGu86pNEF9FPIL7wOO_Qw9XW6BTQkFfqInmzcJaYb45xlexR3gB5t2wUUx86NHoVxGDyE4DzaQp8e1-Qse9foNsCH_X6afb_8ul5-y6_vVlfL8-vcMMp5XjEQBTVQEky1KKmopTYEay1NUQjScAMaG1kZ2EhRMY0buaGFphKLTd0Ump1miznXeBeCh0YN3nbaT4pg9dKreulVHXpNwqdZGMZNB_Urvi8yAZ_3gA5Gt43XvbHhlRMcF0XBEidn7sm2MP1nrLq_uVr--4l8dm2I8Ofgav9L8YpVpXq8XakHtpLryx9rdc_-Asm8pEI</recordid><startdate>200703</startdate><enddate>200703</enddate><creator>Viney, Rebecca L.</creator><creator>Morrison, Avril A.</creator><creator>van den Heuvel, Lambert P.</creator><creator>Ni, Lan</creator><creator>Mathieson, Peter W.</creator><creator>Saleem, Moin A.</creator><creator>Ladomery, Michael R.</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley-VCH</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>200703</creationdate><title>A proteomic investigation of glomerular podocytes from a Denys-Drash Syndrome patient with a mutation in the Wilms tumour suppressor gene WT1</title><author>Viney, Rebecca L. ; Morrison, Avril A. ; van den Heuvel, Lambert P. ; Ni, Lan ; Mathieson, Peter W. ; Saleem, Moin A. ; Ladomery, Michael R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3266-73e842ce5102a8528d9ac10aa9c4481f6cea0c97ceb9873a0f9b24a2908bdf4a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>2-D DIGE</topic><topic>Amino Acid Substitution</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>Child</topic><topic>Cytoskeletal architecture</topic><topic>Denys-Drash Syndrome</topic><topic>Denys-Drash Syndrome - genetics</topic><topic>Denys-Drash Syndrome - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Kidneys</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Podocytes</topic><topic>Podocytes - metabolism</topic><topic>Proteins</topic><topic>Proteome - metabolism</topic><topic>Proteomics</topic><topic>Tumors of the urinary system</topic><topic>WT1</topic><topic>WT1 Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Viney, Rebecca L.</creatorcontrib><creatorcontrib>Morrison, Avril A.</creatorcontrib><creatorcontrib>van den Heuvel, Lambert P.</creatorcontrib><creatorcontrib>Ni, Lan</creatorcontrib><creatorcontrib>Mathieson, Peter W.</creatorcontrib><creatorcontrib>Saleem, Moin A.</creatorcontrib><creatorcontrib>Ladomery, Michael R.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Proteomics (Weinheim)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Viney, Rebecca L.</au><au>Morrison, Avril A.</au><au>van den Heuvel, Lambert P.</au><au>Ni, Lan</au><au>Mathieson, Peter W.</au><au>Saleem, Moin A.</au><au>Ladomery, Michael R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A proteomic investigation of glomerular podocytes from a Denys-Drash Syndrome patient with a mutation in the Wilms tumour suppressor gene WT1</atitle><jtitle>Proteomics (Weinheim)</jtitle><addtitle>Proteomics</addtitle><date>2007-03</date><risdate>2007</risdate><volume>7</volume><issue>5</issue><spage>804</spage><epage>815</epage><pages>804-815</pages><issn>1615-9853</issn><eissn>1615-9861</eissn><abstract>Glomerular podocytes are essential for blood filtration in the kidney underpinned by their unique cytoskeletal morphology. An increasing number of kidney diseases are being associated with key podocyte abnormalities. The Wilms tumour suppressor gene (WT1) encodes a zinc finger protein with a crucial role in normal kidney development; and in the adult, WT1 is required for normal podocyte function. Denys‐Drash Syndrome (DDS) results from mutations affecting the zinc finger domain of WT1. The aim of this study was to undertake, for the first time, a proteomic analysis of cultured human podocytes; and to analyse the molecular changes in DDS podocytes. The morphology of DDS podocytes was highly irregular, reminiscent of a fibroblastic appearance. A reference 2‐D gel was generated, and 75 proteins were identified of which 43% involved in cytoskeletal architecture. The DDS and wild‐type proteomes were compared by 2‐D DIGE. The level of 95.6% of proteins was unaltered; but 4.4% were altered more than two‐fold. A sample of proteins involved in cytoskeletal architecture appeared to be misexpressed in DDS podocytes. Consistent with this finding, overall levels of filamentous actin also appeared reduced in DDS podocytes. We conclude that one of WT1 functions in podocytes is to regulate the expression of key components and regulators of the cytoskeleton.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>17295355</pmid><doi>10.1002/pmic.200600666</doi><tpages>12</tpages></addata></record> |
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subjects | 2-D DIGE Amino Acid Substitution Analytical, structural and metabolic biochemistry Biological and medical sciences Cells, Cultured Child Cytoskeletal architecture Denys-Drash Syndrome Denys-Drash Syndrome - genetics Denys-Drash Syndrome - metabolism Fundamental and applied biological sciences. Psychology Humans Kidneys Medical sciences Miscellaneous Nephrology. Urinary tract diseases Podocytes Podocytes - metabolism Proteins Proteome - metabolism Proteomics Tumors of the urinary system WT1 WT1 Proteins - genetics |
title | A proteomic investigation of glomerular podocytes from a Denys-Drash Syndrome patient with a mutation in the Wilms tumour suppressor gene WT1 |
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